Research news

Insects may possess a hitherto unsuspected molecular complexity in their immune system,
comparable to the antibody system of mammals, scientists report online this week in Science.

"The number of immune receptors might go from a couple of dozen up to thousands in
insects. The complexity there might have really been underestimated," senior author
Dietmar Schmucker, of Harvard Medical School in Boston, told The Scientist.

In the current study, the researchers investigated whether Dscam played a role in immune response. Using reverse transcriptase polymerase chain reaction
(RT-PCR), they found Dscam expression in Drosophila fat body cells, which secrete antimicrobial peptides, and hemocytes, which are involved
in phagocytosis. Using antibodies against extracellular domains of Dscam, they also found a soluble Dscam protein secreted in hemolymph serum.

The ability to generate extensive diversity of immune receptors was generally thought
to be limited to jawed vertebrates. "This diversity of proteins certainly raises the
parallel to antibodies in higher mammals," Brenton Graveley at the University of Connecticut Health Center in Farmington, who did not participate
in this study, told The Scientist. "In mammals, T-cell receptors have recently been found to be expressed in the brain, so this shows another class of molecules that play
an important role in both nervous and immune systems."

Schmucker and colleagues subsequently found that isoforms Dscam-7.27.25-Fc and Dscam-7.27.13-Fc
could bind to live E. coli, while binding of Dscam-1.30.30-Fc was barely detectable. This raises the possibility
that different isoforms might bind specifically to distinct epitopes on bacteria.

"A whole series of new studies are needed to address whether these different isoforms
really are capable of an adapted, specific response to pathogens," Schmucker said.
"We could purify hemocytes out, challenge them with different pathogens and have microarrays
look at Dscam splicing to see if you do upregulate certain isoforms in a predictable way, if you
have a gram-positive infection or a gram-negative one or of yeast." Another open question
these findings raise is whether insects possess immunological memory, he added.

In the end, levels of insect and mammalian immune molecular diversity may reflect
very different lifestyles, Schmucker noted. "Insects live only a few months, some
a few years, so that makes a big impact in how you invest in immunity. Immune receptor
diversity may not be as important there when compared with vertebrates, many of which
live many years," he explained.

"If this is adaptive immunity in insects, it's probably a case of convergent evolution
with mammals," Graveley said. "Both are composed of Ig domains but are very different
structurally and involve very different mechanisms of alternative splicing and gene
rearrangement. And there is a Dscam homolog in mammals that is not alternatively spliced to an appreciable extent."

Given the millions of extant insect species, different spectra of Dscam isoforms likely exist, added Larry Zipursky of the University of California, Los Angeles, who did not participate in this study.
"That might in some way reflect a difference in their susceptibility to pathogens,
and understanding that or even interfering with that may have important implications
for issues of agriculture or of insects that act as vectors for human disease, such
as with mosquitoes and malaria," he told The Scientist.